亚低温减轻氧糖剥夺所致的大鼠海马神经元损伤

 目的： 研究亚低温（31～32　℃）对氧糖剥夺（OGD）损伤的大鼠海马神经元的保护作用并探讨其保护机制。方法：本实验通过体外培养大鼠海马神经元并予以OGD处理,建立了模拟大脑缺血、缺氧的神经元OGD模型;将实验细胞随机分为正常对照组、单纯亚低温组、单纯OGD组以及亚低温+OGD组,通过形态学观察、神经元凋亡率检测以及胞浆内caspase-3活性检测,研究亚低温对神经元OGD的保护作用及其机制。结果：神经元OGD后出现明显的细胞损伤,凋亡率明显升高(P＜0.01);与单纯OGD组比较,亚低温+OGD组细胞损伤明显改善,细胞形态学改善,凋亡率下降(P＜0.05),同时caspase-3活性亦下降(P＜0.05);神经元OGD后caspase-3活性升高,与凋亡率呈正相关（r=0.823,P＜0.05）,神经元经过亚低温和OGD后caspase-3活性与凋亡率亦呈正相关（r=0.841,P＜0.05）。结论：OGD可使caspase-3的活性升高及神经元凋亡率增加。亚低温对神经元OGD的保护作用可能与其抑制caspase-3的活性有关。     

亚低温抑制重型颅脑创伤诱导Tau蛋白过度磷酸化的实验研究

目的 观察亚低温对重型颅脑创伤诱导的Tau蛋白磷酸化的影响.方法 体外研究通过细胞液压冲击仪建立SK-N-SH细胞损伤模型,观察冲击1h、6h和12h后Tau蛋白的磷酸化水平.体内研究通过小动物液压冲击仪建立大鼠重型颅脑损伤模型(2.4 atm),接受或不接受亚低温治疗(33℃,4h).观察液压冲击6h、24 h和72 h后Tau蛋白的磷酸化水平,以及亚低温对此变化的影响.结果 SK-N-SH细胞在液压冲击后,Tau蛋白在Thr231和Ser396位点的磷酸化水平从1h开始升高,到6h左右达到高峰.SD大鼠在液压冲击后,Tau蛋白在Thr231和Ser396位点的磷酸化水平从6h开始升高,到24h左右达到高峰,到72 h仍处于高水平;免疫组化的结果也显示,大鼠脑部海马CA1区和皮质区的Tau蛋白磷酸化水平在Thr231位点也明显增高.亚低温可显著逆转液压冲击诱导的SD大鼠Tau蛋白过度磷酸化(P＜0.01).结论 亚低温可抑制重型颅脑创伤诱导的Tau蛋白过度磷酸化.     

Effects of continuous venovenous haemofiltration-induced cooling on global haemodynamics, splanchnic oxygen and energy balance in critically ill patients.

BACKGROUND: A number of haemodialysis studies have demonstrated beneficial effects of cooler dialysates on global haemodynamics in chronic dialysis patients. However, the effects of continuous venovenous haemofiltration (CVVH)-induced cooling on regional perfusion and energy metabolism in critically ill septic patients have not been well defined. METHODS: Nine septic mechanically ventilated patients (age 40-69 years) were investigated during CVVH (ultrafiltration 30-35 ml/kg/h). Baseline data (=WARM 1) were collected when core temperature (Tc) was >37.5 degrees C; the second data set (=COLD) was obtained after 120 min of 'cooling'; and a third set (=WARM 2) was obtained after 120 min of 'rewarming'. During 'warming' (WARM 1 and 2, respectively), both substitution fluids (SFs) and 'returned' blood (RB) were warmed (37 degrees C), whereas during 'cooling', the SFs were at 20 degrees C and RB was not warmed. We measured hepatic venous (HV) haemoglobin oxygen saturation (ShvO(2)), blood gases, lactate and pyruvate. Gastric mucosal PCO(2) (PgmCO(2)) was measured by air tonometry and the gastric mucosal - arterial PCO(2) difference (PCO(2) gap) was calculated. Haemodynamic monitoring was performed with arterial and pulmonary arterial thermodilution catheters. RESULTS: Tcs were significantly altered [WARM 1, 37.9 degrees C (37.6, 38.3); COLD, 36.8 degrees C (36.3, 37.1); WARM 2, 37.5 degrees C (37.0, 38.0); P<0.001; data are median, 25th and 75th percentiles, respectively]. Systemic vascular resistance significantly increased during cooling. As a result, mean arterial pressure increased. Cooling was associated with significant decreases in heart rate, cardiac output, systemic oxygen delivery and consumption. ShvO(2) did not change [WARM 1, 51.0% (44.0, 59.5); COLD, 49.0% (42.0, 58.0); WARM 2, 51.0% (46.0, 57.0); P = NS]. The splanchnic oxygen extraction ratio, the HV lactate to pyruvate ratio, HV acid base status and PCO(2) gap remained unchanged. CONCLUSION: Mild core cooling induced by CVVH may not affect hepatosplanchnic oxygen and energy balance in septic critically ill patients, even though it affects global haemodynamics.     

低温液体灌注产生亚低温的进展

低温对脑损伤的保护作用已被众多动物实验所证实,在临床方面,尤其是发现轻度和中度低温的保护作用之后,应用逐渐增多.近年来,亚低温被用于治疗新生儿缺氧性脑病、心肺复苏后脑保护、脑外伤及脑卒中等领域.目前临床及实验中所应用的低温方式主要为全身亚低温,如降温毯、冰袋等,这些方式降温效率低,不易迅速实现亚低温,而且全身低温可伴有多种并发症,如心律紊乱、凝血功能障碍等.低温液体或自体血液灌注是目前最有效的降温方式,而且局部动脉内灌注低温液体更可以快速实现局部亚低温.介入技术的进步使得快速局部动脉内低温液体灌注成为可能.我们详细回顾相关动物实验及临床应用文献,介绍低温液体灌注产生亚低温的研究进展.     

亚低温治疗急性重型颅脑损伤的临床观察

目的　观察亚低温治疗急性重型颅脑损伤的疗效 ;探讨亚低温治疗的平稳性和安全性。方法将 1 1 2例急性重型颅脑损伤随机分为亚低温组 (5 5例 )和对照组 (5 7例 )。亚低温组入院后或术后立即给予亚低温治疗 ,酌情运用冬眠合剂、肌松剂和呼吸机 ,肛温控制在 32℃～ 34℃ ,持续 2 4小时～ 5天。对照组给予常规治疗。两组均观察颅内压 (ICP)、生命体征、脑干听觉诱发电位 (BAEP)Ⅰ /Ⅴ波幅比值等的变化。结果　亚低温组经亚低温治疗后 ,ICP下降明显 ;1 1例血压下降 ,1 2例心率减慢 ,复温后 ,以上指标均恢复正常 ;亚低温治疗后 2 4小时及复温后 ,双侧BAEPⅠ /Ⅴ比值与对照组同时段相比差异显著。亚低温组死亡 1 3例 ,死亡率 2 3.6 % ;对照组死亡 2 6例 ,死亡率 4 5 .6 % ,两组有显著性差异。结论　亚低温治疗能降低脑外伤后增高的ICP ,从而使死亡率及致残率明显下降。亚低温治疗中合理使用辅助药物 ,可以保障亚低温治疗的平稳性及安全性     

低温环境下放射性与火器复合伤后细菌学改变的研究

目的观察低温环境下放射性与火器复合伤(下称放火器复合伤)后伤道及血液细菌学变化特点,为其临床救治提供理论依据。方法以30只新西兰大白兔制备低温放火器复合伤动物模型,分别于致伤后0、4、8、16、24、48 h进行实验动物体温变化动态观察,伤道及血液中的细菌定性培养及菌群种类分析。结果低温放火器复合伤动物体温伤后明显升高,伤后4 h平均体温达(39.47±0.39)℃,体温变化趋势非常显著。伤后4 h,伤道局部分泌物中细菌为表面菌群,伤后8 h检测到肠道菌群。血液中出现细菌的时间为伤后8 h,既有表面菌群,又有肠道菌群。结论低温放火器复合伤后体温升高明显,细菌感染较严重,细菌入血时间早,肠道细菌容易入血,处理应尽早清创,早期合理使用广谱抗生素。     

亚低温联合大剂量纳洛酮治疗脑出血的疗效观察

目的探讨亚低温、纳络酮以及两者联合治疗脑出血的疗效及安全性。方法40例急性脑出血患者随机分为4组：对照组10例,发病后给予甘露醇脱水、6一氨基已酸止血等常规治疗;亚低温组10例,在常规治疗的基础上给予亚低温治疗4d,鼻咽温度控制在33—34℃;纳络酮组10例,在常规治疗的基础上给予4mg纳络酮静脉点滴,每日1次,共14d;联合组10例,在常规治疗的基础上给予头颅亚低温治疗和静脉点滴纳络酮。于入院时和治疗第14d行头颅cT扫描,测定出血量和水肿量;并于治疗前、后用欧洲卒中评分量表（ESS）评定患者神经功能。结果治疗前：4组间比较,出血量、水肿量和ESS评分差异均无统计学意义（P〉0．05）。治疗第14d,4组间出血量差异无统计学意义（P〉0．05）;亚低温组水肿量与联合组接近（P〉o．05）,但明显低于纳络酮组（P〈0．05）和对照组（P〈0．05）,纳络酮组明显低于对照组（P〈0．05）。治疗后ESS评分由高到低分别是：联合组、亚低温组、纳络酮组;各组间的分值比较,差并均有统计学意义（P〈0.05）。结论头颅亚低温和纳络酮静脉点滴治疗均能明显减轻脑出血患者的脑水肿,改善其神经功能缺损;亚低温在减轻脑水肿和改善神经功能缺损方面的作用均优于纳络酮;联合应用虽不能进一步减轻脑水肿,但对神经功能缺损的改善作用更明显。     

全身麻醉患儿术后恢复期保温措施研究

目的探讨非气管插管全身麻醉患儿术后转入麻醉恢复室的最佳保温方法。方法选择非气管插管全身麻醉手术后转入麻醉恢复室患儿120例,按随机数字表法分为S1组、S2组和C组各40例。S1组采用加温系统实施主动保温,温度调节为38℃;S2组采用加温毯实施主动保温,温度调节为38℃;C组采用常规盖棉被保暖。观察三组生命体征变化、意识恢复时间、在麻醉恢复室停留时间、低体温及并发症发生率的差异。结果三组不同时间体温和心率比较,干预效应、时间效应均P0.05,交互效应均P0.05。三组术后意识恢复时间、恢复室停留时间、低体温和寒战发生率比较,差异有统计学意义(P0.05,P0.01),S1组各项指标更优。结论对非气管插管全麻手术后患儿在麻醉恢复室实施加温系统主动保温,可以降低术后低体温发生率,有助于患儿尽快恢复。     

Hypothermia attenuates apoptosis and protects contact between myelin basic protein‐expressing oligodendroglial‐lineage cells and neurons against hypoxia–Ischemia

Periventricular leukomalacia (PVL) is a major form of brain injury among preterm infants, which is characterized by extensive loss and dysfunction of premyelinating oligodendrocytes (pre‐OLs) induced by hypoxia–ischemia (HI). Therapeutic hypothermia, which is a standard treatment for term infants with HI encephalopathy, is not indicated for preterm infants because its safety and effect have not been established. Here we investigate the effectiveness and mechanism of hypothermia for the inhibition of pre‐OLs damage in PVL. For in vivo studies, 6‐day‐old rats underwent left carotid artery ligation, followed by exposure to 6% oxygen for 1 hr under hypothermic or normothermic conditions. The loss of myelin basic protein (MBP) was inhibited by hypothermia. For in vitro studies, primary pre‐OLs cultures were subjected to oxygen–glucose deprivation (OGD) under normothermic or hypothermic conditions, and dorsal root ganglion neurons were subsequently added. Hypothermia inhibited apoptosis of pre‐OLs, and, despite specific downregulation of 21.5‐ and 17‐kDa MBP mRNA expression during hypothermia, recovery of the expression after OGD was superior compared with normothermia. OGD caused disarrangement of MBP distribution, decreased the levels of phosphorylated 21.5‐kDa MBP, and disturbed the capacity to contact with neurons, all of which were restored by hypothermia. Pharmacological inhibition of ERK1/2 phosphorylation with U0126 during and after OGD significantly reduced the protective effects of hypothermia on apoptosis and myelination, respectively. These data suggest that phosphorylated exon 2‐containing (21.5‐ and possibly 17‐kDa) MBP isoforms may play critical roles in myelination and that hypothermia attenuates apoptosis and preserves the contact between OLs and neurons via ERK1/2 phosphorylation. © 2014 Wiley Periodicals, Inc.